Impact of COVID-19 on antibiotic prescriptions for Brazilian children

The COVID-19 brought a new model of sanitary behavior (social distancing, etc.) that may have reduced the transmissibility of respiratory diseases, reflecting in the number of antibiotic prescriptions. This study evaluated antibiotic prescriptions for children throughout Brazil, between 2014 and 2021. An interrupted time series was conducted to assess variations in antibiotic consumption by the 1–12-year-old children. Joinpoint regression was used to assess the monthly variations. 86 million prescriptions were evaluated. On average, there was a 54% reduction in prescriptions during the pandemic. Amoxicillin showed a reduction of 65%. Joinpoint regression showed that the pandemic altered the prescription growth curve, changing the trend to a 22% drop per month. The new sanitary behavior showed us that it is possible, decreasing the use of antibiotics, to control the children’s respiratory health.

www.nature.com/scientificreports/ ceftriaxone (4.1%). In addition, we found metronidazole, cefadroxil, levofloxacin, benzylpenicillin-benzathine, and erythromycin in less than 2% of the prescriptions. The data in Fig. 1 reveal a significant reduction in the average monthly consumption of antibiotics during the pandemic (P < 0.0001). Historical data show average sales of around 800,000 units/month in 2014, reaching more than 1 million/month in 2019. However, sales dropped significantly during the Pandemic period (Jan 2020-July 2021), showing a reduction in the monthly average of about 54% in sales (P < 0.0001), reaching 433 thousand units/month.
The data in Table 1 show the monthly averages of units sold for all antibiotics between 2014 and 2019 and during the pandemic period and the variation in sales (%). When comparing the sales of all antibiotics during the pandemic with previous years' averages, they appear to have dropped by 54%. For the most prescribed antibiotic in the country, amoxicillin, the reduction in sales was 65%.
The data in Fig. 2 show the monthly variation in the consumption of the 10 antibiotics most sold in Brazil for children. The blue bars mark the hottest months of the year (summer), making the annual seasonality clear in antibiotic prescriptions for the treatment of respiratory infections (amoxicillin and azithromycin). The figure also marks (in red) the date of the first COVID case in Brazil, coinciding with the abrupt drop in the sale of all antibiotics intended for children. The evaluation using Joinpoint regression (dashed black line) shows, from January 2014, an average monthly growth of 0.4% in the sales of all antibiotics until January 2020, when it marks an average monthly decrease in sales of around 22.3%. The average monthly drop continued until May 2020.

Discussion
We found a significant reduction in the consumption of antibiotics by Brazilian children during the pandemic. Although some studies in adults 9,10 have shown an increase in consumption of azithromycin during the pandemic due to its alleged activity against COVID, these same studies also showed a reduction in the consumption of azithromycin in children of approximately 35% during the study period.
Historical data also show a steady drop (regardless of the pandemic) in erythromycin prescriptions. With an average of 6800 monthly prescriptions in 2014, and practically zero number of units was sold in 2019 and during the pandemic. Certainly, the dosage convenience of azithromycin has overcome the discomfort of 4 daily doses of erythromycin, leading physicians to prescribe azithromycin instead [11][12][13] .
The greatest decreases found in the present study were for amoxicillin (65%) and cephalexin (61%), antibiotics used for respiratory infections in children. This data can also show us that there is a concrete possibility to reduce  www.nature.com/scientificreports/ the consumption of antibiotics in normal situations (without a pandemic). As other similar studies have shown, these data show us that health and educational measures can reduce the need for medical consultations and the consequent prescription of antibiotics 3,3 . In June 2021, with the decrease in cases of covid in Brazil, decrease in social distancing, and winter, average sales began to grow approximately 3.21% per month, continuing until the end date of the study (July 2021). As other authors have shown [14][15][16] , social distancing and the new sanitary habits imposed by the pandemic (masks and hand hygiene) are fundamental for reducing respiratory infections and the consequent use of antibiotics. Although the pandemic has brought countless personal and humanitarian tragedies, it has shown that the new norms of sanitary behavior can be fundamental in reducing the transmissibility of respiratory infectious diseases and the consequent decrease in the consumption of antibiotics. Furthermore, a global decrease in prescriptions and consumption of antibiotics will likely decrease the emergence of new resistant bacteria. Consequently, the likelihood of a new, this time of antibiotic-resistant bacteria, pandemic may decrease.
Our results showed that there was a 54% reduction in the consumption of all classes of antibiotics by children during the pandemic. Hygiene measures, social distancing and the reduction in medical appointments may have contributed to this reduction. Other studies will be carried out with updated data to observe the variations in the number of prescriptions of these same antibiotics after the pandemic period.

Study limitations.
The data from the present study, although very representative, only show the antibiotics consumed by Brazilian children in the community (oral and intramuscular). Data on antibiotic consumption in hospitalized children are not included in the present study as they are not available.

Data availability
The dataset analysed during the current study is public and available from the corresponding author on reasonable request or at the link: https:// dados. anvisa. gov. br/ dados/ SNGPC/ Indus trial izados/.